15-72783505-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001365225.1(ADPGK):​c.187G>A​(p.Ala63Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,465,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A63S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

ADPGK
NM_001365225.1 missense

Scores

1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.11
Variant links:
Genes affected
ADPGK (HGNC:25250): (ADP dependent glucokinase) ADPGK (EC 2.7.1.147) catalyzes the ADP-dependent phosphorylation of glucose to glucose-6-phosphate and may play a role in glycolysis, possibly during ischemic conditions (Ronimus and Morgan, 2004 [PubMed 14975750]).[supplied by OMIM, Mar 2008]
ADPGK-AS1 (HGNC:44144): (ADPGK antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0057326257).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADPGKNM_001365225.1 linkc.187G>A p.Ala63Thr missense_variant Exon 1 of 7 ENST00000456471.3 NP_001352154.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADPGKENST00000456471.3 linkc.187G>A p.Ala63Thr missense_variant Exon 1 of 7 1 NM_001365225.1 ENSP00000397694.3 Q9BRR6-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152224
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000546
AC:
4
AN:
73266
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
41928
show subpopulations
Gnomad AFR exome
AF:
0.000828
Gnomad AMR exome
AF:
0.000214
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000762
AC:
10
AN:
1312944
Hom.:
0
Cov.:
31
AF XY:
0.00000310
AC XY:
2
AN XY:
644988
show subpopulations
Gnomad4 AFR exome
AF:
0.000227
Gnomad4 AMR exome
AF:
0.000159
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000459
AC:
7
AN:
152342
Hom.:
0
Cov.:
33
AF XY:
0.0000537
AC XY:
4
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.000168
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000756
ExAC
AF:
0.0000214
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.187G>A (p.A63T) alteration is located in exon 1 (coding exon 1) of the ADPGK gene. This alteration results from a G to A substitution at nucleotide position 187, causing the alanine (A) at amino acid position 63 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
20
DANN
Benign
0.89
Eigen
Benign
-0.66
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.38
N
LIST_S2
Benign
0.82
T
MetaRNN
Benign
0.0057
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.38
N
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
0.12
N
REVEL
Benign
0.038
Sift
Benign
0.62
T
Sift4G
Benign
0.73
T
Polyphen
0.0030
B
Vest4
0.092
MutPred
0.30
Gain of sheet (P = 0.0061);
MVP
0.41
MPC
0.23
ClinPred
0.059
T
GERP RS
3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs550362727; hg19: chr15-73075846; API